THE ASSOCIATION BETWEEN THE MELANOCYTE‐STIMULATING HORMONE RECEPTOR AND THE α 2 ‐ADRENOCEPTOR ON THE Anolis MELANOPHORE

1 The primary effect of catecholamines was to lighten Anolis skin previously darkened by α‐melanocyte‐stimulating hormone (α‐MSH). In concentrations above 10 −7 m noradrenaline, 10 −6 m adrenaline and 10 −5 m dopamine, darkening of subpopulations of melanophores occurred. Subsequent experiments were concerned with the effect of low catecholamine concentrations on α‐MSH action. 2 The relationship between MSH receptors and α‐adrenoceptors on the Anolis melanophore was studied by a kinetic approach using the rate bioassay method and by use of α‐adrenoceptor agonists and antagonists. 3 α‐MSH dose‐response curves were shifted, in parallel, to the right in the presence of the catecholamines, noradrenaline, adrenaline and dopamine, and Lineweaver‐Burke plots and Arunlakshana‐Schild plots indicated that the catecholamines antagonized MSH action by a competitive mechanism. 4 Phentolamine had an inhibitory effect on the action of adrenaline but not on the action of MSH. Therefore MSH and catecholamine actions were mediated by separate receptors. 5 The classical kinetics of competition are not confined to competition at a single receptor. 6 The α‐adrenoceptor was defined as the α 2 ‐subtype since (a) the α 2 ‐selective agonist, clonidine, was found to mimic catecholamine action. (b) The α 2 ‐selective antagonist, yohimbine, blocked the actions of clonidine and adrenaline. (c) The α 1 ‐selective antagonist, prazosin, had negligible blocking effects on adrenaline and clonidine. 7 We conclude that a close association exists between the separate MSH receptor and α 2 ‐adrenoceptor on the Anolis melanophore. The competition that takes place between MSH and catecholamines must occur after hormone‐receptor interaction, possibly through a common adenylate cyclase moiety oppositely controlled by the two receptors involved.